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Classification of familial amyotrophic lateral sclerosis by family history: effects on frequency of genes mutation
  1. Amelia Conte1,
  2. Serena Lattante2,
  3. Marco Luigetti1,
  4. Alessandra Del Grande1,
  5. Angela Romano1,
  6. Alessandro Marcaccio1,
  7. Giuseppe Marangi2,
  8. Paolo Maria Rossini1,3,
  9. Giovanni Neri2,
  10. Marcella Zollino2,
  11. Mario Sabatelli1
  1. 1Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy
  2. 2Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Rome, Italy
  3. 3IRCCS S. Raffaele-Pisana, Rome and Casa di Cura S. Raffaele Cassino, Rome, Italy
  1. Correspondence to Dr Mario Sabatelli, Istituto di Neurologia. Pol. “A. Gemelli”, Largo A. Gemelli, 8, Rome 00168, Italy; msabatelli{at}


Objective To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories.

Methods Included in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed.

Results Thirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS.

Conclusions Our findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.

  • Familial amyotrophic lateral sclerosis
  • motor neuron disease
  • genetics
  • neuropathy
  • neurophysiol
  • clinical
  • vasculitis
  • neuromuscular
  • evoked potentials
  • somatosensory
  • neurophysiology
  • ALS

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  • Linked article 303127.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the local ethical committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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